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Biochemistry, Biophysics, and Structural Biology Commons

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Electronic Thesis and Dissertation Repository

2015

Apoptosis

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The Epigenetic Regulators Atrx And Ctcf Are Required For Mouse Neuroprogenitor Cell Survival And Brain Development, Lauren Ashley Watson Apr 2015

The Epigenetic Regulators Atrx And Ctcf Are Required For Mouse Neuroprogenitor Cell Survival And Brain Development, Lauren Ashley Watson

Electronic Thesis and Dissertation Repository

Emerging evidence implicates the regulation of higher-order chromatin structure in brain development, maturation, and function. Human mutations in two important regulators of chromatin structure, ATRX and CTCF, cause microcephaly and intellectual disability and have been identified in several cancers, suggesting an important role for these proteins in the developing brain and to suppress tumorigenesis. This thesis demonstrates that chromatin structure is critical to the differentiation and survival of neural progenitor cells, and explores the mechanisms of ATRX and CTCF function in brain development. The first chapter identifies that Atrx deficiency induces replicative DNA damage at telomeres and pericentromeric heterochromatin, and …